Label-Free Detection of DNA Mutations by Nanopore Analysis

Cancers are caused by mutations to genes that regulate cell normal functions. The capability to rapid and reliable detection of specific target gene variations can facilitate early disease detection and diagnosis and also enables personalized treatment of cancer. Most of the currently available methods for DNA mutation detection are time-consuming and/or require the use of labels or sophisticated instruments. In this work, we reported a label-free enzymatic reaction-based nanopore sensing strategy to detect DNA mutations, including base substitution, deletion, and insertion. The method was rapid and highly sensitive with a detection limit of 4.8 nM in a 10 min electrical recording. Furthermore, the nanopore assay could differentiate among perfect match, one mismatch, and two mismatches. In addition, simulated serum samples were successfully analyzed. Our developed nanopore-based DNA mutation detection strategy should find useful application in genetic diagnosis.